Abstract
RationaleEcstasy is a commonly used psychoactive drug with 3,4-methylenedioxymethamphetamine (MDMA) as the main content. Importantly, it has been suggested that use of MDMA may be neurotoxic particularly for serotonergic (5-hydroxytryptamine (5-HT)) neurons. In the past decades, several molecular imaging studies examined directly in vivo the effects of ecstasy/MDMA on neurotransmitter systems.ObjectivesThe objective of the present study is to review the effects of ecstasy/MDMA on neurotransmitter systems as assessed by molecular imaging studies in small animals, non-human primates and humans.MethodsA search in PubMed was performed. Eighty-eight articles were found on which inclusion and exclusion criteria were applied.ResultsThirty-three studies met the inclusion criteria; all were focused on the 5-HT or dopamine (DA) system. Importantly, 9 out of 11 of the animal studies that examined the effects of MDMA on 5-HT transporter (SERT) availability showed a significant loss of binding potential. In human studies, this was the case for 14 out of 16 studies, particularly in heavy users. In abstinent users, significant recovery of SERT binding was found over time. Most imaging studies in humans that focused on the DA system did not find any significant effect of ecstasy/MDMA use.ConclusionsPreclinical and clinical molecular imaging studies on the effects of ecstasy/MDMA use/administration on neurotransmitter systems show quite consistent alterations of the 5-HT system. Particularly, in human studies, loss of SERT binding was observed in heavy ecstasy users, which might reflect 5-HT neurotoxicity, although alternative explanations (e.g. down-regulation of the SERT) cannot be excluded.
Highlights
Ecstasy is a common recreationally used psychoactive drug
To draw conclusions whether MDMA may induce changes in neurotransmitter systems, we offer a review of the results of imaging studies on the effects of ecstasy/MDMA on neurotransmitter systems in small laboratory animals, non-human primates and humans
The included studies examined the effects of ecstasy on 5-HT synthesis, the studies indicated that the 5-HT transporter (SERT), 5-HT2A receptor, 5-HT1A receptor, 5HT-ergic vesicular monoamine transporter
Summary
Ecstasy is a common recreationally used psychoactive drug. The name ecstasy refers to the main effects of the drug, because the Greek word Bεκστασις^ (ekstasis) means Bstanding out of yourself^. People can experience entactogenic effects and feel extremely connected with others and some even have mild hallucinations (Reynolds 2013) These effects are caused by MDMA, the main content of ecstasy tablets, through a mechanism of enhanced release of the neurotransmitter serotonin (5-hydroxytryptamine (5-HT)) as well as a relatively small release of another monoaminergic neurotransmitter, namely dopamine (2-(3,4-dihydroxyfenyl)-ethaanamine (DA)) (Lyles and Cadet 2003). It is well known from animal studies that MDMA administration induces a massive release of 5-HT and that frequent administrations of MDMA may induce neurotoxic effects on the 5-HT system (Commins et al 1987; Lyles and Cadet 2003), administration of MDMA
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